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Case Report A case report on epithelioid inflammatory myofibroblastic sarcoma in the abdominal cavity

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Received June 18, 2019; Accepted August 27, 2019; Epub October 1, 2019; Published October 15, 2019

Abstract: Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare entity and a novel variant of the in -flammatory myofibroblastic tumor (IMT). We report the occurrence and specific characteristics of EMIS in an adult woman. Eleven months after the operation, the patient had a recurrence and multiple metastases in the abdominal cavity. Since the tumor was spreading all over the abdominal cavity and ALK staining of the tumor was positive, crizotinib was suggested as adjuvant therapy. But she failed to respond to the crizotinib treatment and died of organ failure three months later.

Keywords: Epithelioid inflammatory myofibroblastic sarcoma, ALK, crizotinib

Introduction

Inflammatory myofibroblastoma (IMT) is an

interstitial neoplasm composed of myofibro

-blast spindle cells in a mucoid stroma. Its

inflammatory infiltration mainly consists of

plasma cells and lymphocytes, occasionally

mixed with eosinophils and neutrophils [1].

Epithelioid inflammatory myofibroblastic sarco

-ma (EIMS) is a rare entity and a novel variant of

the inflammatory myofibroblastic tumor (IMT),

as it has similar malignant characteristics and

mainly consists of round‑to‑epithelioid cells [2]

with a pattern of nuclear membrane or perinu

-clear immunostaining for ALK receptor tyrosine

kinase (hereafter ALK). EMIS is a rare disease.

To the best of our knowledge, only 30 cases

have been reported in the English-language

medical literature. Herein, we report the

occur-rence and specific characteristics of EMIS in an

adult woman, and the relevant literature is

reviewed. Our report provides further informa

-tion on EMIS.

Case report

The report involves a 46‑year‑old female who

was hospitalized due to left upper abdominal

pain lasting for 3 months and abdominal dis

-tention lasting for 2 months. A CT examination

showed a solid mass in the left upper intra‑

abdomen, which could not be distinguished

from the stomach. When a strengthening scan

was performed, the mass showed non‑uniform

intensification (

Figure 1A

and

1B

). A few irregu

-lar nodules were seen below the mass, and

some were fused into a mass. The larger one

was about 5.6 cm×4.0 cm×5.2 cm in size. The

mass also showed non‑uniform intensification

when a strengthening scan was performed.

A laparotomy indicated that a tumor was detect

-ed in the left upper intra‑abdomen with a size of

11 cm×6.5 cm×7 cm. It was nodular,

encapsu-lated, and with moderate hardness and gray‑

white in the cut surface. Microscopically, the

tumor cells were spindle-shaped or round like,

with mitotic figures of 4/10 HPF. There was a

large number of inflammatory cells infiltrated in

the background, with more collagen bundles,

and pleomorphic hyalinizing angiectasia. A

small area of mucoid degeneration was found

(left inferior phrenic). Multiple lymph nodes

were involved by the tumor (

Figure 2

). Immu-

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[image:2.612.89.527.72.221.2] [image:2.612.92.524.277.473.2]

Figure 1. Computed tomography (CT) revealing a solid mass in the left upper intra‑abdomen (A). When a strengthen -ing scan was performed, the mass showed non‑uniform intensification (B).

Figure 2. Grossly, the huge tumor located in the left upper intra‑abdomen, nodular, encapsulated, and with moder -ate hardness and gray‑white in the cut surface. Microscopically, the tumor cells are spindle‑shaped or round like.

[image:2.612.90.526.529.691.2]
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approximately 20%. CD56, S‑100, CDla, NF,

NSE, Calponin, CD21, CD23, CD117, CD34, and

Dog‑1 were negative. This primary pathology

finding provided a convincing diagnosis of the

inflammatory myofibroblastic tumor (

Figure 3

).

The tumor showed a sheet and nodular growth

pattern, and the stromal mucus changed to-

gether with prominent infiltrated lymphocytes,

neutrophils and eosinophils.

The patient did not have any additional treat

-ment after the operation. Eleven months after

the operation, because of abdominal pain, she

received CT imaging, which displayed a recur

-rent intra-abdominal tumor, and multiple me-

tastases were observed in her liver, ventral

wall, abdominal cavity, pelvic cavity, and uter

-ine appendages (

Figure 4

). Since the tumor

was spreading all over the abdominal cavity

and ALK staining of the tumor was positive

(2p23 ALK gene rearrangement by immunohis

-tochemistry), crizotinib was suggested as adju

-vant therapy. Then crizotinib (200 mg) was

administered to the patient twice a day orally.

The patient’s previous clinical symptoms were

significantly relieved, and the response evalua

-tion reached a partial response (PR) (

Figure 5

).

However, two months later, a CT examination

revealed the progression of the disease (

Figure

6

). The patient failed to respond to the treat

-ment with crizotinib. Accordingly, there was lit

-tle guidance on how to treat EIMS after pro‑

gression on crizotinib. According to the results

of genetic testing, antiangiogenic therapy may

be effective. Thus, we started treatment of giv

-ing anlotinib 12 mg qd for the full two weeks,

and three weeks for a period. Unfortunately, the

antivascular therapy achieved little effect. Due

to the poor general condition of the patient, the

follow‑up treatment gave priority to symptom

[image:3.612.90.524.72.215.2]

-atic supportive treatment. The patient died of

organ failure three months later.

Figure 4. The tumor recurrence eleven months after the operation, and multiple metastases are observed in the liver, ventral wall, abdominal cavity, pelvic cavity, and uterine appendages.

[image:3.612.91.524.265.431.2]
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Discussion

In 2011, Marino Enriquez et al. [2] described in

detail the clinicopathological,

immunohisto-chemical and genetic characteristics of 11

additional cases and named them EIMS to

highlight both the distinct morphology and

malignant behavior of this aggressive form of

IMT. Clinically, EIMS mainly occurs among chil

-dren and adolescents, although the overall age

range varies greatly. Previous studies reported

that the patients’ ages ranged from 7 months

to 65 years, with an average age of 33.4 years

[2‑11]. As a rare malignant mesenchymal neo

-plasm, it is often found in the lung, abdominal/

pelvic and retroperitoneal cavity, regardless of

age [10].

In clinical practice, EIMS is a rapidly growing

abdominal mass or thoracic nodule, which

attracts medical attention when abdominal

pain, ascites or pleural effusion occur. Cases of

reported EIMS have ranged in size from 6 to 26

cm [2, 5, 12]. In some cases, general fatigue

and weight loss are the primary clinical mani

-festations instead of abdominal pain and a pal

-pable nodular lesion [13].

Since cases of EIMS are so rare, the diagnosis

should be only made through a strict histologi

-cal and clini-cal manifestation. Based on the

previously reported cases, the common histo

[image:4.612.91.525.72.237.2]

-logical features of EIMS are abundant myxoid

stroma with inflammatory infiltrating and plump

round‑to‑epithelioid cell morphology. In most of

the cases, frequent immunopositivity for ALK

[2, 5, 12] and the RANBP2‑ALK fusion gene

[13] have also been identified.

ALK is a receptor tyrosine kinase gene located

on chromosome 2p23. The rearrangement of

the gene usually results in the high activity of

the ALK protein, which is closely related to the

expression of the ALK protein through im‑

munohistochemistry [14]. In previous reports,

RANBP2, tropomyosin 3 (TPM3), tropomyosin 4

(TPM4), clathrin heavy chain (CLTC), cysteinyl‑

tRNA synthetase (CARS), 5‑aminoimidazole‑

4‑carboxamide ribonucleotide for myltransfer

-ase/IMP cyclohydrolase (ATIC), and SEC31L1

have been identified to fuse with the ALK gene,

and provide active promoters for the fusion

gene [15-17]. Several reports have suggested

that IMTs with RANBP2‑ALK fusion usually

exhibit an epithelioid/round cell morphology

and follow a more aggressive clinical course

[18, 19]. In this case, we identified a 2p23

ALK gene rearrangement by immunohisto‑

chemistry.

The optimal therapy for EIMS has not been well

established. Surgical resection is considered to

be the mainstay of treatment. In view of the

postoperative adjuvant therapy, the available

experience is very limited. Most of the reported

cases were treated with post-operative

chemo-therapy or radiochemo-therapy, which seemed to have

no significant effect in controlling the rapid

recurrence [2, 3, 12, 20, 21]. Recently, an ALK

inhibitor, crizotinib, has been applied in the

treatment of EIMS with a certain effectiveness

[2, 5, 12, 21, 22].

Thus, in the present case, crizotinib (200 mg)

was administered to the patient twice a day

orally.

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mechanisms of resistance in ALK‑positive

patients and found that many of the resistant

samples had ALK resistant domain mutations.

Chromophilicity is described as a resistance

mechanism. Multiple closed chain rearrange

-ments lead to the loss of the tumor suppres

-sor’s gene function and the enhancement of

carcinogenic fusion function [25]. Most muta

-tions in ALK‑positive cancers involve an ALK

tyrosine kinase domain that targets drug resis

-tance patterns [27]. In fact, each ALK tyrosine

kinase inhibitor is associated with a particular

pattern of ALK resistance mutations [26, 27].

Another less common resistance is to amplify

ALK [27].

A key problem is how to prevent the develop

-ment of drug resistance to ALK inhibitors.

Further studies are needed to be conducted

among EIMS patients. Additionally, further drug

development is imperative for both patient life

expectancy and disease remission. PD‑L1

expression in tumor cells is considered to be a

predictive index of the tumor response to immu

-nomodulatory therapies targeting the PD‑1/

PD‑L1 pathway [28], as staining for the pro

-grammed death‑ligand 1 (PD‑L1) is diffusely

positive in the case of EIMS [29].

The expression of PD‑L1 in EIMS indicates an

immune check-point blockade, representing a

novel anti‑EIMS therapy.

Disclosure of conflict of interest

None.

Address correspondence to: Zhiguang Wang, De- partment of Oncology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No 89‑9 Dongge Road, Nanning 530000, Guangxi, China. Tel: +86‑18587904369; E‑mail: a1860@126.com

44.

[3] Li J, Yin WH, Takeuchi K, Guan H, Huang YH and Chan JK. Inflammatory myofibroblastic tu -mor with RANBP2 and ALK gene rearrange -ment: a report of two cases and literature re -view. Diagn Pathol 2013; 8: 147.

[4] Liu Q, Kan Y, Zhao Y, He H and Kong L. Epithe -lioid inflammatory myofibroblastic sarcoma treated with ALK inhibitor: a case report and review of literature. Int J Clin Exp Pathol 2015; 8: 15328-32.

[5] Kimbara S, Takeda K, Fukushima H, Inoue T, Okada H, Shibata Y, Katsushima U, Tsuya A, Tokunaga S, Daga H, Okuno T and Inoue T. A case report of epithelioid inflammatory myofi -broblastic sarcoma with RANBP2‑ALK fusion gene treated with the ALK inhibitor, crizotinib. Jpn J Clin Oncol 2014; 44: 868-71.

[6] Kurihara‑Hosokawa K, Kawasaki I, Tamai A, Yo -shida Y, Yakushiji Y, Ueno H, Fukumoto M, Fu -kushima H, Inoue T and Hosoi M. Epithelioid inflammatory myofibroblastic sarcoma respon‑ sive to surgery and an ALK inhibitor in a patient with panhypopituitarism. Intern Med 2014; 53: 2211-4.

[7] Zhou J, Jiang G, Zhang D, Zhang L, Xu J, Li S, Li W, Ma Y, Zhao A and Zhao Z. Epithelioid inflam -matory myofibroblastic sarcoma with recur -rence after extensive resection: significant clinicopathologic characteristics of a rare ag -gressive soft tissue neoplasm. Int J Clin Exp Pathol 2015; 8: 5803-7.

[8] Wu H, Meng YH, Lu P, Ning HY, Hong L, Kang XL and Duan MG. Epithelioid inflammatory myofi -broblastic sarcoma in abdominal cavity: a case report and review of literature. Int J Clin Exp Pathol 2015; 8: 4213-9.

[9] Bai Y, Jiang M, Liang W and Chen F. Incomplete intestinal obstruction caused by a rare epithe -lioid inflammatory myofibroblastic sarcoma of the colon: a case report. Medicine (Baltimore) 2015; 94: e2342.

(6)

molecular cytogenetic analysis of five addition -al cases and review of the literature. Diagn Pathol 2016; 11: 67.

[11] Jiang Q, Tong HX, Hou YY, Zhang Y, Li JL, Zhou YH, Xu J, Wang JY and Lu WQ. Identification of EML4‑ALK as an alternative fusion gene in epi -thelioid inflammatory myofibroblastic sarcoma. Orphanet J Rare Dis 2017; 12: 97.

[12] Kozu Y, Isaka M, Ohde Y, Takeuchi K and Naka -jima T. Epithelioid inflammatory myofibroblas -tic sarcoma arising in the pleural cavity. Gen Thorac Cardiovasc Surg 2014; 62: 191‑4. [13] Fu X, Jiang J, Tian XY and Li Z. Pulmonary epi

-thelioid inflammatory myofibroblastic sarcoma with multiple bone metastases: case report and review of literature. Diagn Pathol 2015; 10: 106.

[14] Cook JR, Dehner LP, Collins MH, Ma Z, Morris SW, Coffin CM and Hill DA. Anaplastic lympho -ma kinase (ALK) expression in the inflam-ma -tory myofibroblastic tumor: a comparative im -munohistochemical study. Am J Surg Pathol 2001; 25: 1364-71.

[15] Lawrence B, Perez‑Atayde A, Hibbard MK, Ru -bin BP, Dal Cin P, Pinkus JL, Pinkus GS, Xiao S, Yi ES, Fletcher CD and Fletcher JA. TPM3‑ALK and TPM4‑ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol 2000; 157: 377-84.

[16] Cools J, Wlodarska I, Somers R, Mentens N, Pedeutour F, Maes B, De Wolf‑Peeters C, Pau -wels P, Hagemeijer A and Marynen P. Identifi -cation of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large‑cell lymphoma and inflammatory myofi -broblastic tumor. Genes Chromosomes Cancer 2002; 34: 354-62.

[17] Debiec‑Rychter M, Marynen P, Hagemeijer A and Pauwels P. ALK‑ATIC fusion in urinary blad -der inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003; 38: 187-90. [18] Gleason BC and Hornick JL. Inflammatory myo

-fibroblastic tumours: where are we now? J Clin Pathol 2008; 61: 428-37.

[19] Chen ST and Lee JC. An inflammatory myofibro -blastic tumor in liver with ALK and RANBP2 gene rearrangement: combination of distinct morphologic, immunohistochemical, and ge-netic features. Hum Pathol 2008; 39: 1854‑8. [20] Ma Z, Hill DA, Collins MH, Morris SW, Sumegi J,

Zhou M, Zuppan C and Bridge JA. Fusion of ALK to the Ran‑binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003; 37: 98‑ 105.

[21] Butrynski JE, D’Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Ca -pelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Jänne PA, Maki RG, Demetri GD and Shapiro GI. Crizotinib in ALK‑rearranged inflammatory myofibroblastic tumor. N Engl J Med 2010; 363: 1727‑33. [22] Tothova Z and Wagner AJ. Anaplastic lympho

-ma kinase‑directed therapy in inflam-matory myofibroblastic tumors. Curr Opin Oncol 2012; 24: 409-13.

[23] Gainor JF and Shaw AT. Emerging paradigms in the development of resistance to tyrosine ki -nase inhibitors in lung cancer. J Clin Oncol 2013; 31: 3987-96.

[24] Gainor JF, Dardaei L, Yoda S, Friboulet L, Lesh -chiner I, Katayama R, Dagogo‑Jack I, Gadgeel S, Schultz K, Singh M, Chin E, Parks M, Lee D, DiCecca RH, Lockerman E, Huynh T, Logan J, Ritterhouse LL, Le LP, Muniappan A, Digumar -thy S, Channick C, Keyes C, Getz G, Dias‑Santa -gata D, Heist RS, Lennerz J, Sequist LV, Benes CH, Iafrate AJ, Mino‑Kenudson M, Engelman JA and Shaw AT. Molecular mechanisms of resis -tance to first‑ and second‑generation ALK in -hibitors in ALK‑rearranged lung cancer. Cancer Discov 2016; 6: 1118-1133.

[25] Parker BM, Parker JV, Lymperopoulos A and Konda V. A case report: pharmacology and re -sistance patterns of three generations of ALK inhibitors in metastatic inflammatory myofibro -blastic sarcoma. J Oncol Pharm Pract 2019; 25: 1226-1230.

[26] Rotow J and Bivona TG. Understanding and tar -geting resistance mechanisms in NSCLC. Nat Rev Cancer 2017; 17: 637-658.

[27] Attarian S, Rahman N and Halmos B. Emerging uses of biomarkers in lung cancer manage -ment: molecular mechanisms of resistance. Ann Transl Med 2017; 5: 377.

[28] Berger R, Rotem‑Yehudar R, Slama G, Landes S, Kneller A, Leiba M, Koren‑Michowitz M, Shi -moni A and Nagler A. Phase I safety and phar -macokinetic study of CT‑011, a humanized antibody interacting with PD‑1, in patients with advanced hematologic malignancies. Clin Can-cer Res 2008; 14: 3044-51.

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Figure

Figure 1. Computed tomography (CT) revealing a solid mass in the left upper intra‑abdomen (A)
Figure 4. The tumor recurrence eleven months after the operation, and multiple metastases are observed in the liver, ventral wall, abdominal cavity, pelvic cavity, and uterine appendages.
Figure 6. CT examination reveals the progression of the disease (PD) three months after crizotinib.

References

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